Reactions that monitor biochemical processes without interfering with them, known as bioorthogonal reactions, have become important research tools. An addition to the bioorthogonal toolbox might now be available. To develop the new tool, Xiaoguang Lei of China’s National Institute of Biological Sciences and his team adapted chemistry typically used to immobilize molecules on surfaces. That approach joins an o-naphthoquinone methide to various groups, including thiols. But generating the methide requires ultraviolet light, which can damage tissues. Lei’s team instead made o-quinolinone quinone methides that avoid the UV light requirement. Quinone methides have a reputation for cell toxicity, but the researchers observed none in this case. In addition, they used vinyl thioethers, which are rare in biology, as coupling partners in place of thiols. When they souped up versions of the methide-thioether combination with the cancer drug Taxol and a dye, they were able to use fluorescence microscopy to watch Taxol act on microtubules in cancer cells (J. Am. Chem. Soc., DOI: 10.1021/ja401989p). Vladimir V. Popik of the University of Georgia, who developed the original chemistry, likes how the technique can be used alongside other bioorthogonal reactions such as azide-alkyne click chemistry. He next would like to see Lei’s team trick cells into incorporating the thioethers into their own biomolecules, a common practice with click reactions.